A Class Effect Network Meta-analysis of Lipid Modulation in Non-alcoholic Steatohepatitis for Dyslipidemia

Background and Aims: Pharmaceutical therapy for NASH is associated with lipid modulation, but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness. A network meta-analysis was conducted to compare NASH drug classes in lipid modulation. Methods: Online databases were searched for randomized controlled trails (RCTs) evaluating NASH treatments in biopsy-proven NASH patients. Treatments were classified into four groups: (1) inflammation, (2) energy, (3) bile acids, and (4) fibrosis based on the mechanism of action. A Bayesian network analysis was conducted with outcome measured by mean difference (MD) with credible intervals (Crl) and surface under the cumulative ranking curve (SUCRA). Results: Fortyfour RCTs were included in the analysis. Bile acid modulating treatments (MD: 0.05, Crl: 0.03-0.07) were the best treatment for improvement in high-density lipid (HDL) cholesterol, followed by treatments modulating energy (MD: 0.03, Crl: 0.02-0.04) and fibrosis (MD: 0.01, Crl: -0.12 to 0.14) compared with placebo. The top three treatments for reduction in triglycerides were treatments modulating energy (MD: -0.46, Crl: -0.49 to -0.43), bile acids (MD: -0.22, Crl: -0.35 to -0.09), and inflammation (MD: -0.08, Crl: -0.13 to -0.03) compared with placebo. SUCRA found treatment modulating fibrosis (MD: -1.27, Crl: -1.76 to -0.79) was the best treatment for reduction in low-density lipid (LDL) cholesterol followed by treatment modulating inflammation (MD: -1.03, Crl: -1.09 to -0.97) and energy (MD: -0.37, Crl: -0.39 to -0.34) compared with placebo, but LDL cholesterol was worsened by treatments modulating bile acids. Conclusions: Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of atherogenic dyslipidemia. Future studies are required to evaluate the cardiovascular outcomes.